Phenolic Compounds as Arginase Inhibitors: New Insights Regarding Endothelial Dysfunction Treatment

Planta Med. 2018 Mar;84(5):277-295. doi: 10.1055/s-0044-100398. Epub 2018 Jan 17.


Endothelial dysfunction is characterised by the low bioavailability of nitric oxide with a relevant negative impact on the nitric oxide/cGMP pathway. The loss of nitric oxide/cGMP signaling may be caused by an increased arginase activity. Plant-derived substances, especially polyphenols, are compounds that have the potential to inhibit arginase activity and they may represent an attractive therapeutic option to combat clinical outcomes related to endothelial dysfunction. An extensive review was carried out using all available data published in English in the Pubmed database, and without restriction regarding the year of publication. Despite the increased number of new substances that have been tested as arginase inhibitors, it is rare to find a compound that satisfies all the toxicological criteria to be used in the development of a new drug. On the other hand, recent data have shown that substances from plants have great potential to be applied as arginase inhibitors, most of which are polyphenols. Of the relevant mechanisms in this process, the inhibition of arginase by natural products seems to act against endothelial dysfunction by reestablishing the vascular function and elevating nitric oxide levels (by increasing the amounts of substrate (L-arginine, and endothelial nitric oxide synthase activation and stabilisation) as well as decreasing the generation of reactive species (formed by uncoupledendothelial nitric oxide synthase). This review summarises several topics regarding arginase inhibition by natural substances as well as indicating this pathway as an emergent strategy to elevate nitric oxide levels in disorders involving endothelial dysfunction. In addition, some aspects regarding structural activity and future perspectives are discussed.

Publication types

  • Review

MeSH terms

  • Arginase / antagonists & inhibitors*
  • Arginase / metabolism
  • Biological Products / chemistry
  • Biological Products / pharmacology*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiopathology
  • Molecular Structure
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type III / drug effects
  • Nitric Oxide Synthase Type III / physiology
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Plants / chemistry*
  • Polyphenols / chemistry
  • Polyphenols / pharmacology*
  • Structure-Activity Relationship
  • Vascular Diseases / drug therapy*
  • Vascular Diseases / physiopathology


  • Biological Products
  • Plant Extracts
  • Polyphenols
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III
  • Arginase